tbuckley/cabot-search huggingface dataset:
A retrospective analysis of tislelizumab and GP regimen neoadjuvant therapy followed by concurrent chemoradiotherapy plus nimotuzumab in patients with high-risk nasopharyngeal carcinoma.
Authors: Qinhua Zhang, Mingfen Lai, Fangming Li, Jiarong Chen, Mingzhang Chang, Peixin Yang, Guojian Chen
Journal: Journal of Clinical Oncology (2023)

e18060 Background: Efficacy of nasopharyngeal carcinoma (NPC) with T4 or N3 remains unsatisfactory due to high-risk of distant metastasis or recurrence, indicating the need of more comprehensive treatment. We aim to analysis the efficacy and safety of tislelizumab and GP regimen in combination with neoadjuvant therapy and concurrent chemoradiotherapy (CCRT) plus nimotuzumab in patients with high-risk NPC. Methods: Our team conducted a retrospective analysis of 44 adult patients with high-risk locally advanced (T4 or N3; M0) nasopharyngeal carcinoma between March 2021 and January 2022, the median follow-up time was 599 days. The patients had received neoadjuvant chemotherapy (gemcitabine,1000 mg/m 2 , days 1 and 8, cisplatin,80 mg/m 2 , day 1), and tislelizumab (200mg) on day 1 every 3 weeks for 4 cycles followed by chemoradiotherapy including intensity modulated radiotherapy (IMRT), lobaplatin and nimotuzumab. Lobaplatin was intravenously administered at a dose of 30 mg/m 2 on days 1 and 22. Nimotuzumab was intravenously administered at a dose of 200 mg on day 1 every week for 6 weeks. All patients underwent response assessments during neoadjuvant therapy, chemoradiotherapy and follow-up at regular intervals. Results: 44 patients were identified with the median age being 50y(24y-70y). At neoadjuvant treatment period, 44 patients completed 170 cycles of the combination of tislelizumab and GP regimen. During concurrent chemo-radiotherapy period, 42 (95.45%) of 44 patients completed 6 weeks of nimotuzumab treatment and 41 (93.18%) of 44 patients completed 2 cycles of lobaplatin treatment. Overall, 20 patients (45.5%) had a complete response, and 24 (54.5%) had a partial response after neoadjuvant therapy before the start of chemoradiotherapy. At 3 months and 6 months after radiotherapy, 90.9% (40 of 44) and 97.7% (43 of 44) of the patients had a complete response. 42 of the 44 patients were alive (95.5%). 3 events of recurrence(1) or death(2) were recorded. 19 (43.2%) of 44 patients had grade 3-4 treatment-related adverse events, and grade 3-4 immune-related adverse events(irAE) was recorded in 3 patients (6.8%) in the entire treatment. Grade 3-4 irAEs were rash(2) and hypothyroidism(1). Conclusions: Neoadjuvant therapy with tislelizumab and GP regimen followed by concurrent chemoradiotherapy plus nimotuzumab seems to have promising efficacy, lower toxic effects and better treatment compliance, which is a new treatment strategy for high-risk NPC.
<sup>68</sup>Ga-FAPI-46 PET for cancer imaging: A prospective single-arm clinical trial.
Authors: Wolfgang P. Fendler, Timo Bartel, Kim M. Pabst, Rainer Hamacher, Nader Hirmas, Robert Seifert, Stefan Kasper, Michael Nader, Claudia Kesch, Bastian von Tresckow, Christoph Berliner, Sherko Kuemmel, Philipp Harter, Anke C. Reinacher-Schick, Celine Lugnier, Waldemar Uhl, Boris A. Hadaschik, Jens T. Siveke, Viktor Grünwald, Ken Herrmann
Journal: Journal of Clinical Oncology (2023)

3064 Background: Fibroblast activation protein (FAP) is expressed at high levels on tumor associated fibroblasts. FAP-directed radioligand positron-emission-tomography (FAP-PET) is a novel diagnostic tool for cancer. However, we currently do not understand the diagnostic performance of FAP-PET as compared to standard FDG-PET. Here we aim to compare tumor detection by FDG- vs. FAP-PET with independent validation of discrepant findings. Methods: Patients with (a) proven or suspected malignancy, (b) longest tumor diameter &gt;1 cm, (c) intended surgery or biopsy, and (d) no prior external beam radiation or systemic tumor therapy within 3 months underwent FDG- and FAP-PET for tumor localization on subsequent days. Clinical reads were analyzed prospectively on a per-patient and per-region basis (local, locoregional nodal, distant organ or soft tissue, bone). Discrepant findings were validated as true vs. false positive by histopathology or image follow-up. Tracer uptake in tumor tissue was assessed by SUVmax. Results: In total n=100 patients (median 62 years, male/female n=68/32) underwent FDG- and FAP-PET. Five most frequent tumor entities and respective median FDG vs FAP uptake were RCC (n=19; SUVmax 8.4 vs. 7.1), sarcoma (n=18; 10.3 vs. 10.9), NSCLC (n=10; 12.4 vs. 13.7), lymphoma (n=9; 18.3 vs. 10.9), and PDAC (n=8; 4.1 vs. 7.3). On a per-patient basis, FDG- vs FAP-PET localized malignancy in n=93/94 patients. FDG- vs FAP-PET was concordant for the assessment of 362/400 (91%) regions. n=16/400 (4%) regions were negative on FDG- and positive on FAP-PET (88% true, 12% false positive). n=22/400 (6%) regions were negative on FAP- and positive on FDG-PET (57% true, 43% false positive). Two false positive FDG-PET findings were due to tracer uptake in reactive lymph nodes. There were no PET-related adverse events. Conclusions: In patients with various tumor entities, standard FDG- and novel FAP-PET localized tumor equally well. Additionally, FAP-PET was associated with a lower rate of false positive findings, especially in lymph node assessments. Clinical trial information: NCT05160051 . [Table: see text]
Open versus robotic-assisted radical cystectomies: A risk analysis.
Authors: Rishabh Simhal, Kerith Ruoyao Wang, Yash Shah, Daniel P Simon, James Ryan Mark, Mihir S Shah, Leonard G. Gomella, Thenappan Chandrasekar, Costas D. Lallas
Journal: Journal of Clinical Oncology (2023)

4593 Background: Radical cystectomy (RC) is standard of care for muscle-invasive bladder cancer, but it comes with significant perioperative risk with half of patients experiencing major postoperative complications. Robot-assisted radical cystectomies (RARC) have aimed to decrease patient morbidity and have become increasingly adopted in North America. Currently, both open radical cystectomies (ORC) and RARC are frequently performed. To contribute to the existing literature using newly available data from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP), representing one of the most recent, largest multi-institutional studies, while uniquely accounting for a variety of factors including type of urinary diversion, cancer staging, and neoadjuvant chemotherapy. Methods: RC procedures performed between 2019-2020 were identified in NSQIP and the corresponding Cystectomy Targeted database. Cases in the ORC group were planned open procedures, and cases in the RARC group were robotic with intra- or extracorporeal diversions, including unplanned conversion to open cases for intention-to-treat. Chi-square and t-tests were performed to compare baseline demographics and operative parameters. Multivariate analysis was performed for outcomes including major complications, minor complications, and 30-day mortality, while adjusting for operative approach, medical comorbidities, functional status, age, race, sex, BMI, ASA-classification, preoperative labs, type of urinary diversion, pathological staging, prior pelvic surgery or radiation, need for preoperative transfusion, preoperative sepsis, emergent or elective surgery, and recent chemotherapy. Results: 4,022 RC cases were identified. Of these, 3,146 (78.2%) received planned ORC while 876 (21.8%) received RARC. Baseline demographics of the patients who received ORC versus RARC were largely similar, with no significant difference in age or medical comorbidities. RARC was associated with longer operative times and shorter hospital length of stay compared to ORC. On multivariate analysis, ORC was associated with a higher rate of 30-day mortality [OR 3.1; 95% CI 1.3-7.2; p=0.009], reintubation, cardiac arrest, superficial wound infection, bleeding requiring transfusion [OR 4.7; 95%CI 3.6 - 6.1; p&lt;0.001], prolonged postoperative nasogastric tube use, rectal injury, and ureteral fistula or urine leak compared to RARC. Conclusions: In the NSQIP database, ORC is associated with higher rates of 30- day mortality and operative complications, most notably bleeding, compared to RARC. This study is unique in the size of the cohorts compared, the timeliness of the data (2019-2020), and the ability to control for factors, such as type of urinary diversion, pathological bladder cancer staging, and use of neoadjuvant chemotherapy.
Intratumoral heterogeneity as a predictive biomarker in immunotherapy for advanced bladder cancer.
Authors: Haige Chen, Lei Qian
Journal: Journal of Clinical Oncology (2023)

e16619 Background: Previous studies have shown that intra-tumor heterogeneity (ITH) can lead to drug resistance to tumor therapy, which is associated with poor prognosis of solid tumors. However, studies on the correlation between ITH and immunotherapy efficacy in patients with advanced bladder cancer (BLCA) are still lacking. Methods: Bioconductor R package Maftools was used to analyze somatic variants of advanced BLCA from an independent cohort (Miao-249 study cohort, PMID: 30150660) with data from 27 patients who underwent whole-exome sequencing. The ITH score was measured using the mutant-allele tumor heterogeneity (MATH) algorithm to analyze the difference in the genetic profile between the ITH score high (ITH-H) and ITH score low (ITH-L) groups, its association with tumor mutational burden (TMB), and the effect of ITH on the prognosis of immunotherapy. Results: There were significant differences in gene mutation spectrum between ITH-H and ITH-L groups. The genes with the highest mutation frequency in ITH-H group were TP53 (57.14%), DNAH5 (38.1%), TNRC18 (38.1%), TTN (38.1%), CSMD3 (33.33%), MDN1 (33.33%), MRPL49 (33.33%), and MUC19 (33.33%), while the genes with the highest mutation frequency in ITH-L group were KDM6A (83.33%), TP53 (66.67%), CALN1 (50%), MICAL2 (50%), MTOR (50%), NINL (50%), PCDHA (50%), and RMIBP2 (50%). The objective response rate (ORR) of immunotherapy was 66.66% and 42.86% for the patients with ITH-L and ITH-H subgroup. The ITH-L patients had significantly improved median overall survival (mOS) than the ITH-H group (not reach versus 12.3 months, hazard ratio (HR) = 6.65, 95%CI 0.86−51.36, P = 0.037). There was no significant difference in median TMB levels between ITH-L and ITH-H groups (8 Muts/Mb versus 7.6 Muts/Mb, P = 0.97). The TMB high (TMB-H) patients had no significantly better mOS than the TMB low (TMB-L) group (not reach versus 9.07 months, HR = 0.33, 95%CI 0.07−1.49, P = 0.13). A pooled analysis of ITH and TMB show that mOS in the ITH-L+ TMB-H group was numerically better than that in the ITH-H+TMB-H, ITH-H+TMB-L, and ITH-L+TMB-L group (not reach versus 15.6 months versus 7.1 months versus not reach, HR-1.57, 95CI 0−Inf, P = 0.1). Conclusions: The results suggest that ITH may be independent of TMB and a positive predictor of immunotherapy in patients with advanced BLCA.
High dose methotrexate (MTX) treatment: Value of post treatment MTX level monitoring and risk factors for acute kidney injury.
Authors: Rose Snyder, Anna Urazov, Mayukh Deh, Ajinkya Kulkarni, Pin-Jung Chen, Gagan Raju, Miss Tanni, Yiqing Xu
Journal: Journal of Clinical Oncology (2023)

e19539 Background: High-dose methotrexate therapy is an effective treatment for primary central nervous system (CNS) lymphoma and other tumors. Methotrexate (MTX) is an antimetabolite which penetrates blood brain barrier when administered intravenously at high doses. Defective or delayed clearance of MTX may lead to toxicities, especially acute kidney injury (AKI) in 2-13% of patients. We developed a protocol to mitigate side effects by checking MTX levels every 24 hours, administering leucovorin or glucarpidase rescue, and hydration with urine alkalization. This study examines the risk factors for developing AKI after high dose MTX administration. Methods: Patients who began treatment with high dose methotrexate in 2020 and 2021 were eligible. We collected data on demographics, diagnosis, methotrexate levels, laboratory levels at baseline and after treatment, toxicities, interventions and outcomes. Results: 26 patients were included, who received 112 cycles of treatments (median 3.5, range 1-10). Median age was 62 years (range 25-83) and 57% were male. 20 patients experienced elevated MTX levels. Among the 112 cycles, MTX levels were elevated at 24h, 48h and 72h in 22 (19.6%), 16 (14.3%), and 45 (40.2%) of the cycles respectively, which trigged an increase in the rescue leucovorin dose and hydration dose in 26 (23.2%) and 16 (14.3%) cycles, respectively. AKI was recorded in 20 cycles (17.9%), with 17 (85%) being grade 1 (ULN – 1.5 x ULN), and 3 (2.7%) being grade 2 (1.5-3x ULN). In 20 cycles with AKI, 9 (45%) had grade 1 elevated creatinine level pretreatment; 8 (88.9%) of them remained grade1 without increase &gt; 0.2. The development of AKI occurred in all MTX dose levels, without a difference in frequency. 57% of cycles with elevated 24h MTX level, and 13% of cycles with delayed clearance &gt; 4 days, were associated with AKI. 75% of cycles with AKI had delayed clearance (avg 7 days). Two patients required glucarpidase rescue treatment, based on elevated 24-36 h MTX level and grade 1-2 AKI; one of these patients permanently discontinued MTX. Conclusions: Among 26 patients who received a total of 112 cycles of high dose MTX treatment, 11 developed AKI in 20 cycles, mostly grade 1 with spontaneous recovery. MTX level elevation at 24 hours predicted the development of AKI. Elevated baseline creatinine or MTX dose range is not a risk factor for AKI.
Efficacy-effectiveness gap with immune checkpoint inhibitors in solid cancers: A population based cohort study.
Authors: Saroj Niraula
Journal: Journal of Clinical Oncology (2023)

6625 Background: Immune checkpoint inhibitors (ICIs) have been central in oncology drug development in the last decade often demonstrating large improvements in overall survival (OS) in pivotal randomized controlled trials (RCTs). Patient selection and/or care may be less stringent in the real world but ascertaining that benefits are translated satisfactorily from pivotal RCTs into the real world is crucial, as patients often base their treatment decisions on outcomes quoted to them from pivotal RCTs. Methods: After necessary ethics approvals, we collected relevant data on all consecutive patients with advanced solid cancers treated with ICIs in the province of Manitoba, Canada from inception to June 30, 2022 using pharmacy database and cancer registry. Eight most frequent ICI indications are included here. Survival probabilities were plotted using Kaplan-Meier Method, and descriptive statistics used to report relationship between variables. To put outcomes into perspective, we report real world data alongside that of pivotal RCTs used to support approvals of respective ICIs by Health Canada and the US FDA. Results: Eight ICI indications included 992 patients followed for a median of 40 months (range: 21-86 months). Patients required to meet precise provincial formulary criteria to receive ICIs, adopted mostly from the inclusion criteria of the corresponding pivotal RCTs. Median OS was shorter in the real world population not only compared to the experimental arms of the respective pivotal RCTs [by a median of 16 months (range: 3 - 38 months)] but also compared to their control arms [by a median of 3 months (range 3 to 32 months)]. This translated into an average of 51.1% (standard deviation: 20.1) compromise in median OS with ICIs in the real world compared to that observed in respective pivotal RCTs. Conclusions: Treatment with ICIs within high standards of practice in a Canadian province overall offered less than half the median OS observed in pivotal RCTs supporting their approvals. Current ICI treatment decisions by patients (and physicians) may therefore be based on highly inaccurate expectations. Our results should inspire rigorous phase IV clinical studies to identify pertinent real-world variables affecting outcomes including treatment related morbidity and mortality, with an ultimate aim to narrow the alarming efficacy-effectiveness gap. [Table: see text]
Final results of a pilot study of docetaxel and carboplatin for treatment of patients with mCRPC containing biallelic inactivation of genes in the homologous recombination DNA repair pathway.
Authors: Ruben Raychaudhuri, Makayla DeJong, Evan Y. Yu, Roman Gulati, Matthew Rettig, Peter Nelson, Colin C. Pritchard, Robert Bruce Montgomery, Heather H. Cheng
Journal: Journal of Clinical Oncology (2023)

5054 Background: Inactivating mutations in genes important in homologous recombination DNA repair (HRD) are present in the tumors of ~25% of patients with metastatic castration resistant prostate cancer (mCRPC). These alterations are associated with more aggressive disease but may also predict vulnerability to DNA damaging agents. We previously reported promising interim results from a single arm, Phase 1/2 trial studying the combination of the DNA damaging agent carboplatin with docetaxel for patients with mCRPC containing HRD mutations. Here we report final results after completing accrual and two additional years of follow up. Methods: We assessed response to the combination of docetaxel 60mg/m 2 and carboplatin AUC 5 IV q21 days in patients with mCRPC whose tumors had evidence of biallelic inactivation of genes involved in HRD and who had progressed on any prior treatment, including docetaxel and/or PARP inhibitor (PARPi). The primary endpoint was the proportion of patients who achieved ≥50% PSA decline from baseline (PSA 50 ). With H0 of PSA 50 of 26%, 14 patients provided 80% power to conclude H1 of PSA 50 of 60% based on Simon's 2-stage design with 1-sided α = 5%. The secondary endpoints included PSA 30 , response duration, progression-free survival (PFS), and overall survival (OS). Results: The trial opened in Jan 2016 and completed in Sep 2021. A total of 16 patients were treated on study, including 6 who had previously received PARPi and 5 who had received docetaxel. 11/16 patients (69%) achieved PSA 50 . 7/9 patients (78%) with biallelic inactivation of BRCA2 (7), BRCA1 (1), or PALB2 (1) achieved PSA 50 . Other biallelic inactivated HRD-related genes were ATM (1), CHD1 (1), CDK12 (3), MRE11A (1), and NBN (1). Of these patients, 4/7 (57%) achieved PSA 50 . Notably, 3/6 patients (50%) previously treated with PARPi therapy achieved PSA 50 . The median PFS was 8.4 months, and the median OS was 2 years. 6/16 patients (38%) had grade 3 AEs, most commonly thrombocytopenia (25%) and anemia (13%). One patient (6%) had a grade 4 AE (thrombocytopenia). Conclusions: The addition of carboplatin to docetaxel significantly improved response rates in patients with mCRPC with biallelic inactivation in genes involved in the HRD pathway. Responses were also seen in patients who had previously received PARPi. The combination was relatively safe and well-tolerated. The encouraging activity and favorable toxicity profile observed here merits further investigation. Additional work is ongoing to further refine biomarkers predictive of treatment response and resistance. Clinical trial information: NCT02598895 .
Colorectal cancer screening and treatment before and during the COVID-19 pandemic at a Southeast Texas community hospital.
Authors: Ahmed Abdelhakeem, Muhammad Siddiqi, Nigil Thaimuriyil, Chelsey Peters, Samantha Blevins, Tahir A. Naqvi
Journal: Journal of Clinical Oncology (2023)

e15522 Background: The COVID-19 pandemic imposed significant restraints on healthcare systems, raising concerns regarding care delays and excess cancer-related deaths. We aimed to investigate the impact of COVID-19 on colorectal cancer (CRC) screening and the time to treatment initiation (TTI) for cases with a confirmed diagnosis of CRC. Methods: We conducted a retrospective study in which we included all patients who underwent screening colonoscopy between April 2019 and March 2021 at our hospital. Patients with a diagnosis of CRC have been confirmed with the data from our cancer center to check if they could continue cancer staging workup and start their treatment. Patients were stratified into pre-COVID-19 (April 2019-March 2020) and COVID-19 (April 2020-March 2021) groups. Descriptive statistics and multivariate regression analysis were applied using SAS software, version 9.4. Results: A total of 1439 patients underwent screening colonoscopies during the study period. 746 during pre-COVID-19 group, and 693 during COVID-19 group (p = 0.1624). In the pre-COVID-19 group, 47 patients were found to have CRC, and 25 patients (53%) continued cancer staging workup and started treatment in our cancer center. Among 36 patients with confirmed CRC diagnosis in the COVID-19 group, only five patients (14%) continued cancer staging workup and started treatment (p = 0.0003). All patients with confirmed CRC in the COVID -19 group had localized disease compared to 25 patients (96%) in the pre-COVID-19 group. TTI in the COVID-19 group (mean of 21 days ± 13.3) was shorter compared to the pre-COVID-19 group (mean of 33 days ± 46.7) (p = 0.025). Comparative analysis between the study groups didn’t show any statistically significant difference based on age, sex, race, or insurance status. Conclusions: In our hospital, the COVID-19 pandemic didn’t appear to affect the accessibility to CRC screening or delay in TTI. However, a limited number of patients with confirmed CRC during the COVID-19 pandemic were able to continue cancer staging workup and receive treatment.
The long journey of patients with anal carcinoma in a Mexican cohort.
Authors: Javier Alejandro Martinez Moyano, Roberto Adrián Reyna de la Garza, Eduardo Rey Torres-Cisneros, David Hernandez Barajas, Daneli Ruiz Sanchez, Alan Burguete-Torres, Adelina Alcorta Garza, Juan Francisco González Guerrero, Oscar Vidal-Gutiérrez
Journal: Journal of Clinical Oncology (2023)

e15504 Background: Yearly 1000 new cases of anal cancer will be diagnosed in the USA, in Mexico this information is limited. Increasing incidence is the reflection of improvements in knowledge of risk factors and diagnostic studies. Female sex, HPV infection, genital warts, number of sexual partners, receptive anal intercourse, smoking and HIV infection are well established risk factors. Methods: We performed a retrospective analysis of patients with pathology-confirmed anal carcinoma treated at an Oncology Reference Center in North-East Mexico from 2010 to 2020. Using the digital database of our center we searched the time passed since debut of symptoms to first medical contact, date of biopsy and first oncology consultation. Results: 81 patients were found in the database from January 2010 to December 2020. Forty-one patients were included in the final analysis, 11 patients where reassessed as rectal cancer and 29 patients only attended one consultation and did not continue follow up. Mean age at diagnosis was 61.4 +/- 13.8 years and 58.5% were women. 69% of patients had an education degree lower than highschool. HIV status was known only in 9.8% as they were living with HIV before the diagnosis of anal cancer was made, contrasting from 63.4% of cases who had unknown status at cancer diagnosis. The time from symptom onset until the patient attended a healthcare provider was a mean of 7.6 months (5 – 1000 days) and 11.4 months (9-1435 days) to receive a diagnosis. Patients had an average delay of 80 days from biopsy result to be evaluated by an oncologist. 44% of patients were initially misdiagnosed as hemorrhoids. None of the female patients had history of recent Pap smear test. 65% of patients had nodal involvement at presentation. Conclusions: There is notable delay between the onset of symptoms and diagnosis of anal cancer. This information is crucial for the general population and all healthcare providers not only oncology related workers. The stigma as well as the cultural barriers associated with this disease may negatively impact the prognosis and quality of life by delaying promptly treatment. Although it is a rare disease, conducting educational campaigns with the intention of improving clinical suspicion and an early recognition may shorten the long journey of patients bearing with anal carcinoma.